The relationship between renal perfusion pressure and sodium excretion plays an important role in regulating body fluid volumes and arterial pressure. In animal models of essential hypertension, the pressure-natriuresis relationship appears to be altered in such a manner that the "hypertensive" kidney excretes less sodium and water for a given level of renal perfusion pressure. The objective of the present proposal is to examine the role of renal interstitial hydrostatic pressure in this altered pressure-natriuresis relationship and to determine the nephron sites responsible for the enhanced sodium reabsorption. Whole kidney clearance and micropuncture techniques will be used to assess functional renal derangements in two animal models of essential hypertension. The models to be used are the spontaneously hypertensive rat (SHR) and the Dahl salt sensitive hypertensive rat (Dahl S). To obtain a further understanding of the relationship between renal perfusion pressure and sodium excretion, this proposal will also examine the effects of direct increases in renal interstitial hydrostatic pressure on sodium excretion, utilizing a technique (developed by PI) which directly increases renal interstitial hydrostatic pressure by injecting isoncotic saline into the renal interstitium via chronically implanted polyethylene matrix capsules. Specific questions to be addressed are: 1) Is the altered pressure-natriuresis relationship in the SHR and Dahl S rats due to high renal vascular resistance associated with reduced renal interstitial hydrostatic pressure? 2) Are the effects of direct increases in renal interstitial hydrostatic pressure on sodium excretion blunted in the SHR and Dahl S rats? 3) Which nephron site is involved in the enhanced sodium reabsorption in the SHR and Dahl S rats? 4) Which nephron site is affected by direct increases in renal interstitial hydrostatic pressure? Are deep nephrons more sensitive to changes in renal interstitial hydrostatic pressure than superficial nephrons? Answers to these questions should provide new information relevant to the understanding of the basic mechanism involved in the altered relationship between renal perfusion pressure and urinary sodium excretion in animal models of hypertension closely resembling human essential hypertension.